Downloaded 42 times
More Related Content
![Cell signaling -_introduction[1]](https://cdn.slidesharecdn.com/ss_thumbnails/cellsignaling-introduction1-160424161032-thumbnail.jpg?width=640&height=640&fit=bounds)
Cell signaling
- 1.
- 2. Induction: proximate interactions •Close range interactions • Inducer – Tissue doing the inducing – Emits a signal • Secreted peptides • Cell associated proteins • Responder – Tissues/cells that receive the signal – Change as a result of receiving signal – Express receptor to interact with secreted signaling molecule
- 3. Induction • Competence – Theability of a group of cells to respond to the inducing signal – Essentially means competent cells have receptors and all necessary second messengers necessary to respond appropriately to the signal
- 4. Types of InductiveInteractions • Instructive interactions – Signals cause a response – Signals are required for the response – A specific response is induced – Ligand-receptor interactions setting off signal cascade • Permissive interactions – Signals allow a response – Signals do not designate a specific response – ECM allows differentiation
- 5. Examples of Embryonic Inductions •Primary inductions – Mesoderm induction – Neural induction • Secondary inductions – Lens – Retina – Epidermal (hair, scales, feathers) – Tooth – Many organs
- 6. Sequential Inductive Interactions inEye Formation
- 7. Sequential Inductive Interactions inEye Formation Lens induction in amphibians
- 8. Sequential Inductive Interactions inEye Formation Lens & retina formation in rodents 9 9.5 10.5 11.5 13
- 9. Epithelial-Mesenchymal Interactions • Epithelial cells –Cells of epidermal or endodermal origin – have distinct epithelial morphology • Mesenchymal cells – Cells of mesodermal origin – Have a distinct mesenchymal morphology
- 10. Mesenchymal-Epithelial Interactions Epidermis is competent todifferentiate into epidermal structures (follicles). The dermis is the source of inducing signals to specify the type of epidermal structure formed.
- 11. Mesenchymal-Epithelial Interactions Epithelial tissue canonly respond within the limits of its genetic programming. The age old question - Does a chicken have lips?
- 12. Mechanisms of Inductive Signaling •Paracrine signaling – Secreted, diffusible signaling molecules • Peptide growth factors (PGFs) or peptide inducing factors (PIFs) • Not exactly the same as hormones – not secreted into bloodstream but into intercellular space • Signaling at a limited distance • Juxtacrine signaling – Non-soluble signaling molecules • Integral or membrane associated proteins • Signaling occurs at point of cell-cell contact
- 13. Mechanisms of Inductive Signaling ParacrineSignaling Juxtacrine Signaling
- 14. Secreted Signaling Molecules •FGF Family • Hedgehog Family • Wnt Family • TGFβ Superfamily – TGFβ Family – Activin Family – BMP Family • EGF Family • PDGF Family • Retinoids • HGF/Scatter Factor • Neurotrophins • Semaphorins • Cytokines
- 15. Receptors for SolubleSignaling Molecules • Receptor Tyrosine Kinase (RTK) pathway – FGFR, EGFR, PDGFR – Receptor coupled to ras signal transduction cascade • Smad pathway – Bipartite Serine/Threonine Kinase Receptors – AcRI/II, TGFβRI/II, BMPRI/IIs – Receptors activate Smad transcription factors • Wnt-β-catenin pathway – Frizzled family of receptors – Activation of pathway allows β- catenin to enter nucleus • JAK-STAT pathway – Peptide hormone or cytokine receptor coupled to a Jak cytoplasmic tyrosine kinase – Jaks activate STAT transcription factors • Hedgehog Pathway – Patched and smoothened co- receptors – Activation of pathway converts Ci txn’l repressor to activator • Steroids/Retinoids – Nuclear/DNA binding receptors – Hormone permits entry into nucleus, alters DNA binding conformation, or allows interaction with co-txn factors
- 16. Cell Associated Signaling Molecules •ECM (ligand) – Fibronectin – Laminin – Type IV collagen • Integrins (receptor) • CAMs (receptor) •Notch Family (receptor) •Delta Family (ligand) •Eph Family (receptor) •Ephrin Family (ligand)
- 17.
- 18. RTK- Ras Pathway GAP Grb2,Shc GEFlike Sos GEF
- 19. Evolutionary Conservation ofRas Pathway
- 20. Examples of RTKSignaling: Photoreceptor Differentiation
- 21. Examples of RTKSignaling: Photoreceptor Differentiation sev = sevenless boss = bride of sevenless ro = rough
- 22. Examples of RTKSignaling: Vulval Differentiation in C. elegans
- 23. Critical Mutations InRTK Pathways • Constitutively active receptors • Dominant negative receptors • Constitutively active Ras • Faulty GEFs or GAPs
- 24.
- 25. Smad Pathway • Mesodermspecification – TGFβ - activin, Vg1, nodal • Ectoderm specification – BMP4, 7 • Dorsal specification (Drosophila) – Dpp
- 26. Smad Pathway Inhibitors •Inhibitory Smads – Bind to smads 1, 5 or 2, 3 in the hypophosphorylated state & prevent interaction with smad4 – Phosphorylation of smads 1,5, 2 & 3 disrupt inhibitory smad interaction and allow smad 4 binding • Noggin • Chordin – Bind to BMPs and prevent their interaction with receptors
- 27. Smad Pathway A MoreDetailed Look
- 28. Wnt - β-catenin Pathway Amore detailed look at Wnt signaling
- 29. • Wnt =Drosophila wingless (wg) + mammalian int-1 ∀β-catenin = armadillo • Dorsal specification in Xenopus • Segment polarity in Drosophila Wnt - β-catenin Pathway
- 30. • Inhibitors ofwnt signaling – Frisbee – Dickkopf – Cerberus • Look like extracellular portion of frizzled • Bind to wnts and prevent their interaction with frizzled Wnt - β-catenin Pathway Inhibitors
- 31.
- 32. JAK-Stat Pathway • Cytokinereceptors – Interleukin, Interferon receptors – Blood cell differentiation • Chondrocyte differentiation • Mammary epithelium
- 33. Juxtacrine Signaling: NotchPathway
- 34. Lateral Inhibition Specification ofneural precursor cells in Drosophila neurectoderm Blue cell becomes neural precursor – GMC; white ones remain epidermis.
- 35.
- 36.
- 37.
- 38. Eph RTK/Cell Adhesion Interactions& Signaling Eph receptor
- 39.